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1.
Int J Infect Dis ; 124: 49-54, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2105076

ABSTRACT

OBJECTIVES: The objective was to estimate the seroprevalence of SARS-CoV-2 in autumn 2019 (before case zero was identified in Italy) and 2021 among residual sera samples from health care users in the Piedmont region of northwestern Italy. METHODS: Two serosurveys were conducted. Using a semiquantitative method, samples were tested for the presence of immunoglobulin G (IgG) antibodies against the S1 domain of the spike protein. Samples with positive test results from the 2019 survey were independently retested using a multiplex panel to detect IgG antibodies against the receptor binding domain, S1 and S2 domains, and nucleocapsid. Samples with positive test results from the 2021 survey underwent repeat testing with enzyme-linked immunosorbent assay to detect anti-nucleocapsid IgG antibodies. Prevalence rates according to gender and age groups, together with their respective 95% confidence intervals (CIs), were calculated. RESULTS: Overall, the proportion of samples with positive test results was 2/353 in 2019 and 22/363 in 2021, with an estimated seroprevalence of 0.27% (95% CI 0-1.86) and 6.21% (95% CI 3.9-9.31) in 2019 and 2021 respectively. CONCLUSION: Results of this study support the hypothesis that the virus was circulating in Italy as early as autumn 2019. The role of these early cases in broader transmission dynamics remains to be determined.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Seroepidemiologic Studies , COVID-19/epidemiology , Antibodies, Viral , Immunoglobulin G , Delivery of Health Care
2.
Front Cardiovasc Med ; 9: 1012452, 2022.
Article in English | MEDLINE | ID: covidwho-2099118
3.
Cureus ; 14(9): e29296, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2072206

ABSTRACT

Background Patients with chronic kidney disease and undergoing hemodialysis are at greater risk of developing COVID-19. In spite of vaccine efficacy, SARS-CoV-2 breakthrough infection has been reported in several studies. This study was carried out to assess if seroconversion could predict SARS-CoV-2 breakthrough infection in a cohort of vaccinated patients undergoing hemodialysis. Methodology Patients undergoing maintenance hemodialysis for at least three months and who had received two doses of BBV152 or AZD1222 vaccine were included in the study. Their baseline IgG antibodies to SARS-CoV-2 were measured and followed up for a median of three months during the third wave of COVID-19 in India with SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) to detect breakthrough infections. Results Of 80 patients enrolled, seroconversion was seen in 81% of the cases, and SARS-CoV-2 breakthrough cases have been detected in 16% (13/80; 95% CI 8.95-26.18) patients undergoing hemodialysis. Of the 13 patients, seven patients required hospitalization and others had a mild outcome. There was no correlation of baseline seropositivity with breakthrough infections or hospitalization. Conclusions A majority of patients who underwent hemodialysis are seropositive post-vaccination. The breakthrough infection did not correlate with baseline seroconversion. Thus, there would be other predictors of breakthrough COVID-19 infections that need to be recognized in this susceptible population.

4.
Int J Mol Sci ; 23(20)2022 Oct 17.
Article in English | MEDLINE | ID: covidwho-2071517

ABSTRACT

Transmembrane glycoprotein integrins play crucial roles in biochemical processes, and by their inhibition or activation, different signal pathways can be disrupted, leading to abnormal physiological functions. We have previously demonstrated the inhibitory effect of glyphosate herbicide's active ingredient on cell adhesion and its αvß3 integrin antagonist effect. Therefore, it appeared particularly exciting to investigate inhibition of glyphosate and its metabolites on a wider range of Arg-Gly-Asp (RGD) binding integrins, namely αvß3, α5ß1 and αllbß3. Thus, the purpose of this study was to assess how extended the inhibitory effect observed for glyphosate on the integrin αvß3 is in terms of other RGD integrins and other structurally or metabolically related derivatives of glyphosate. Five different experimental setups using enzyme-linked immunosorbent assays were applied: (i) αvß3 binding to a synthetic polymer containing RGD; (ii) αvß3 binding to its extracellular matrix (ECM) protein, vitronectin; (iii) α5ß1 binding to the above polymer containing RGD; (iv) αllbß3 binding to its ECM protein, fibrinogen and (v) αvß3 binding to the SARS-CoV-2 spike protein receptor binding domain. Total inhibition of αvß3 binding to RGD was detected for glyphosate and its main metabolite, aminomethylphosphonic acid (AMPA), as well as for acetylglycine on α5ß1 binding to RGD.


Subject(s)
COVID-19 , Herbicides , Humans , Integrin alphaVbeta3/metabolism , Vitronectin , Herbicides/pharmacology , SARS-CoV-2 , Oligopeptides/chemistry , Enzyme-Linked Immunosorbent Assay , Fibrinogen , Polymers
5.
Journal of Clinical and Diagnostic Research ; 16(9):ED01-ED03, 2022.
Article in English | EMBASE | ID: covidwho-2067193

ABSTRACT

Sickle Cell Disease (SCD) is an inherited disorder with variable clinical presentation and low immunity. Coronavirus Disease-2019 (COVID-19)is a pandemic disease with a high-risk in chronic disease patients and older adults. SCD is widely distributed in Sudan;many SCD patients are infected with COVID-19. Despite this, no published data is available. This case report demonstrated the haematological and clinical course of a Sudanese sickle cell anaemia patient with COVID-19. A 20-year-old male patient was admitted to a hospital for 15 days. Demographic and clinical data were obtained from his medical records. A blood sample was taken at the time of admission and during hospitalisation. Tests were performed during admission, including Complete Blood Count (CBC), liver function test, renal function test, coagulation studies, viral screening, and urine general. The patient was diagnosed with COVID-19 using the Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test based on the nasopharyngeal swab and COVID-19 IgG and IgM using Enzyme Linked Immunosorbent Assay (ELISA) for the previous infection. The patient received intravenous fluids, antibiotics, analgesia, oxygen supplementation, and blood transfusion two times during hospitalisation, and there was no need for Intensive Care Unit (ICU) admission. The patient's prognosis was good;he was discharged on day 16 with no symptoms and a negative result of the COVID-19 PCR test. A severe illness was expected because he was infected twice by COVID-19, the patient showed mild clinical symptoms with a good prognosis, so further studies are required to understand COVID-19 among Sudanese SCD patients.

6.
Journal of Clinical and Diagnostic Research ; 16(8):44-47, 2022.
Article in English | EMBASE | ID: covidwho-2067192

ABSTRACT

Introduction: The emergence of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) as a pandemic has put the global population at risk for its infection. It has also led to an accelerated effort to develop vaccines that can mitigate progression to severe infections at a minimum. The ambiguity about existence of antibodies in the human serum poses problem in formulating public health policies like suitable interval between doses of vaccines, appropriate time for vaccinating population, post natural infection, necessity of booster doses along with single dose. Aim: To estimate neutralising antibody level following vaccination of Healthcare Workers (HCWs) after three months and six months respectively. Materials and Methods: This was a prospective observational study performed in Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India after Institutional Ethics Committee (IEC) approval from January 2021 to February 2022. The study was conducted in 304 HCWs in the institute who had received two doses of Recombinant ChAdOx1 nCoV- 19 Corona Virus Vaccine (Covishield). 41 HCWs who were naturally infected with SARS-CoV-2 either before or after vaccination were also included. These participants were then subjected to IgG neutralising antibody titer estimation at three months and six months, postvaccination. Results: The study included 304 eligible HCWs. Majority of the participants belonged to the age group of 31-40 years (35.9%). Majority of the study participants were females (51%). Of the 304 participants, 263 were uninfected and 41 participants had been infected before and after vaccination. At the six month follow-up, it was observed that all but one HCW had seroconverted with majority of the participants showing more than 60% antibody level. Participants in the age group of 31-40 years showed the highest level and this observation was found to be statistically significant. Conclusion: Neutralising antibody response in HCWs is a key indicator of the efficacy of the vaccination program for Coronavirus Disease-2019 (COVID-19) in India.

7.
Open Access Macedonian Journal of Medical Sciences ; 10:2029-2033, 2022.
Article in English | EMBASE | ID: covidwho-2066705

ABSTRACT

BACKGROUND: Mycobacterium tuberculosis infection causes the release of pro-inflammatory cytokines affecting hemostasis. Although the plasminogen activator inhibitor-1 (PAI-1) has a vital role in the fibrinolysis system, little is known about its profile among people with latent tuberculosis (TB). METHODS: This is a cross-sectional study that involves 80 healthcare workers. The study was conducted in two academic medical centers of Makassar city, Indonesia, from September to October 2021. PAI-1 levels were measured using the enzyme-linked immunosorbent assay technique. The statistical test results were significant if p < 0.05. RESULTS: Although there was no statistically significant difference (p > 0.05) in PAI-1 levels, PAI-1 level among participants in the latent TB infection (LTBI) group was found to be lower (4.9 ng/mL) than in the healthy control group (6.0 ng/mL). In addition, participants in the LTBI group with a history of being infected (9.6 ng/mL) with the COVID-19 had higher PAI-1 levels than those who had never been infected (2.3 ng/mL), which is statistically significant (p = 0.004). Although there was no statistically significant difference (p > 0.05) in PAI-1 levels among participants in the healthy control group, those with a history of being infected (6.7 ng/mL) demonstrated higher PAI-1 levels than those who had never been infected (4.8 ng/mL). CONCLUSIONS: PAI-1 levels were lower in LTBI participants, which potentially is due to more participants in the healthy control group having a history of COVID-19 infection.

8.
American Journal of Transplantation ; 22(Supplement 3):638-639, 2022.
Article in English | EMBASE | ID: covidwho-2063546

ABSTRACT

Purpose: Solid organ transplant recipients (SOTR) develop weak antibody responses after SARS-CoV-2 vaccination. Published data on neutralizing activity of plasma, a better measure of protection, in SOTR following an additional dose of SARSCoV- 2 vaccine is limited. Method(s): Plasma was longitudinally collected from SOTR following initial COVID- 19 vaccination. Neutralizing activity against SARS-CoV-2 was assessed using the cPass Neutralization Antibody Detection Kit (GenScript, Biotech). ELISAs were performed against SARS-CoV-2 proteins (S1, N, RBD), CMV (glycoprotein B), Influenza A H1N1 (nucleoprotein), HSV-1, EBV glycoprotein (gp350), and tetanus toxoid for comparison. Result(s): Demographic and clinical characteristics are summarized in table 1. No participants had evidence of COVID-19 infection as IgG titers to SARS-CoV-2 N protein were low. Neutralizing activity against SARS-CoV-2 RBD was observed in 39.6% of individuals (N=21/53) ~93 days after initial vaccination. Participants with neutralizing activity were more likely to have received a liver transplant (47.6% vs 6.25%, p=0.001), and less likely to be on an anti-metabolite (52.4% vs. 87.5%, p=0.009) or triple immunosuppression (14.3% vs. 53.1%, p=0.008). After an additional vaccine dose, 78.1% (N=25/32) of participants developed neutralizing activity with significant increases in viral neutralization (figure 1, median 36.8% [95%CI 18.9-64.6] to 97.2% [95%CI 74.0-98.9], p<0.0001). Participants with low neutralizing activity demonstrated adequate antibody titers to other microbial antigens (figure 2). Conclusion(s): An additional dose of SARS-CoV-2 vaccine increased the number of SOTR with neutralizing activity and the magnitude of the seroresponse. SOTR with low neutralizing activity maintain humoral responses to other microbial antigens suggesting the diminished seroresponse might be related to inhibition of new B cell responses.

9.
American Journal of Transplantation ; 22(Supplement 3):1066, 2022.
Article in English | EMBASE | ID: covidwho-2063501

ABSTRACT

Purpose: Solid organ transplant (SOT) recipients mount suboptimal immune responses to a two-dose SARS-CoV-2 mRNA vaccine series. Data regarding antibody responses in HIV and SOT remains limited. We characterized spike binding antibody responses before and after an additional mRNA vaccine dose in SOT recipients, including in people with HIV (PWH). Method(s): Spike binding antibody titers were assessed before and one month after an additional vaccine dose using a quantitative ELISA. An additional vaccine dose was defined as a third dose of a mRNA vaccine primary series, as recommended by the CDC. Result(s): Antibody titers were assessed in 64 SOT recipients (58% kidney, 34% liver, 8% other). Participants had a median age of 57 and 47% were women. PWH comprised 14% of the cohort (9/64, 78% kidney). 70% (45/64) of SOT recipients developed antibodies after a two-dose vaccine series (62% kidney, 33% liver). The additional dose was given a median of 169 days (IQR 144.75-185.75 days) after the second vaccine dose, and 72% received three doses of BNT162b2 (Pfizer-BioNTech) while 28% received three doses of mRNA-1273 vaccine (Moderna). The median time between transplantation and an additional vaccine dose was 2.8 years (IQR, 0.6-8.9). 32% (6/19) of SOT recipients who had no detectable antibody seroconverted after receiving an additional vaccine dose. The 45 participants who were seropositive prior to the third dose displayed a median 4.4-fold increase in antibody titers. SOT recipients with HIV had comparable antibody responses to those without HIV. Conclusion(s): Our data indicate that SOT recipients benefit from an additional SARS-CoV-2 mRNA vaccine dose. SOT recipients with and without HIV appear to mount comparable antibody responses upon vaccination, although larger numbers are needed.

10.
American Journal of Transplantation ; 22(Supplement 3):1065, 2022.
Article in English | EMBASE | ID: covidwho-2063473

ABSTRACT

Purpose: SARS-CoV-2 is associated with high mortality among transplant recipients. Data of transplant patients' infections post-2nd vaccine dose is not available. The aim of the study was to establish the extend to which vaccinated patients were protected from severe infection. Method(s): We recruited 920 kidney transplant patients receiving at least one dose of SARS-CoV-2 vaccine (Astra-Zeneca-AZ or Pfizer) excluding patients with known virus pre-exposure. Serological status was determined using the COVIDSeroKlir enzyme-linked-immunosorbent-assay (ELISA) (Kantaro-EKF). Patients with corrected antibody level less than 0.7AU/mL were considered seronegative. All SARS-CoV-2 infections post-2nd and up to 2-weeks post the third dose were recorded. We considered severe the infections requiring admission and moderate the infections lasting over 10 days or requiring A&E (ER) attendance without admission. Result(s): 593 patients had their samples analysed post-second dose. 42.8% of AZ patients seroconverted (148/346) compared to 52.6% of Pfizer (130/247, p=0.02, HR 1.07-2.06). There were 53 PCR-confirmed infections between 1/7/21 and 20/11/21, 33 in AZ and 18 in Pfizer patients. Two patients had received no vaccine and 3 patients who received AZ had no specimen for analysis. 10 patients' infection was over 6 months post-2nd dose.41/315 (13%) of seronegative patients got infected compared to 7/278 (2.5%) of seropositive patients (p=0.00001, OR 5.9 CI 2.554- 13.139) during this period.There were 15 mild, 5 moderate, and 13 severe infections post AZ and 11 mild, 3 moderate, 4 severe post Pfizer respectively. 16/17 patients admitted and 7/8 with moderate disease had no demonstrable antibody response at their latest sample post-2nd vaccine dose. There were 2 deaths. We observed at least 3 seropositive patients who became seronegative and got infection. Conclusion(s): 5.5% of vaccinated and 13% of seronegative transplant patients got SARS-CoV-2 infection following the 2nd vaccine dose. 92% of patients with moderate/severe disease were seronegative. A significant proportion of transplant patients remains at risk of serious illness due to SARS-CoV-2 because they do not demonstrate an antibody response to vaccination.

11.
American Journal of Transplantation ; 22(Supplement 3):637-638, 2022.
Article in English | EMBASE | ID: covidwho-2063471

ABSTRACT

Purpose: Solid organ transplant recipients (SOTRs) are at increased risk for severe COVID-19 and exhibit lower antibody responses to SARS-CoV-2 vaccines. This study aimed to determine if pre-vaccination cytokine levels are associated with antibody response to SARS-CoV-2 vaccination. Method(s): A cross-sectional study was performed among 58 SOTRs before and after two-dose mRNA vaccine series, 35 additional SOTRs before and after a third vaccine dose, with comparison to 16 healthy controls (HCs). Anti-spike antibody was assessed using the IgG Euroimmun ELISA. Electrochemiluminescence detectionbased multiplexed sandwich immunoassays were used to quantify plasma cytokine and chemokine concentrations (n=20 analytes). Concentrations between SOTRs and HCs, stratified by ultimate antibody response to the vaccine, were compared using Wilcoxon-rank-sum test with false discovery rates (FDR) computed to correct for multiple comparisons. Result(s): In the study population, 100% of HCs, 59% of SOTRs after two doses and 63% of SOTRs after three doses had a detectable antibody response. Multiple baseline cytokines were elevated in SOTRs versus HCs. There was no significant difference in cytokine levels between SOTRs with high vs low-titer antibodies after two doses of vaccine. However, as compared to poor antibody responders, SOTRs who went on to develop a high-titer antibody response to a third dose of vaccine had significantly higher pre-third dose levels of several innate immune cytokines including IL-17, IL-2Ra, IL-6, IP-10, MIP-1alpha, and TNF-alpha (FDR <0.05). Conclusion(s): A specific inflammatory profile or immune state may identify which SOTRs are likely to develop stronger sero-response and possible protection after a third dose of SARS-CoV-2 vaccine.

12.
American Journal of Transplantation ; 22(Supplement 3):768, 2022.
Article in English | EMBASE | ID: covidwho-2063440

ABSTRACT

Purpose: Short-term adaptive immune memory has been reported among immunocompetent (IC) and convalescent Solid Organ Transplant (SOT) individuals following SARS-CoV-2 infection as well as after active vaccination. However, quality and longevity of anti-viral immune memory comparisons between natural and active immunization has not been thoroughly assessed among SOT. Method(s): SARS-CoV-2-specific adaptive immune memory was assessed at different compartments (serological, memory B cells [mBC] and cytokine [Th1: IFN-gamma, IL-2, IFN-gamma/IL-2 and Th2: IL-21 and IL-5] producing T cells) by ELISA and FluoroSpotbased assays, respectively, in 41 convalescent patients with severe COVID-19 (22 SOT and 19 IC) and 39 vaccinated patients (19 SOT and 20 IC) with a mRNA-based vaccine) at different time-points post immunization (T1=21days after infection/1st dose;T2=3months after infection/2nd dose;T3=6months after infection/2nd dose). Additionally, a group of convalescent mild (19 SOT and 19 IC) and asymptomatic patients (9 SOT and 10 IC) were also evaluated at T3. Result(s): Overall, statistically significant higher immune responses in all immune compartments were observed in convalescent patients than among those after vaccination. After vaccination, low seropositivity rates (5,88%) were observed among SOT after 1st dose, whereas seroconversion was fully achieved in IC patients and SOT with severe COVID-19 (p<0.001). Similarly, while the presence of mBc after vaccination progressively increased over time, it was less pronounced and significantly delayed among SOT than convalescent patients in all time points (p<0.001 T1, T2 and T3). SARS-CoV-2-specific Th1 and Th2 frequencies were significantly higher among vaccinated IC patients than SOT, being these responses significantly lower than those observed in convalescent among SOTT and IC patients (p<0.001 T1, T2 and T3). At 6 months after vaccination, IgG titers, mBc frequencies and Th1/ Th2 T-cell responses after two-dose vaccination in SOT mimicked those observed in convalescent SOT with an asymptomatic/mild clinical COVID-19 infection. Conclusion(s): The type of immunization against SARS-CoV-2, either natural or active after vaccination, clearly differentiates the quality and length of adaptive immune memory, with a clear weaker immune response observed among SOT.

13.
American Journal of Transplantation ; 22(Supplement 3):1059-1060, 2022.
Article in English | EMBASE | ID: covidwho-2063422

ABSTRACT

Purpose: Kidney transplant recipients (KT) and wait-listed individuals exhibit an impaired response to vaccinations. There is currently no data on the impact of induction immunosuppression followed by standard immunosuppression on the antibody (Ab) dynamics of wait-listed individuals undergoing KT. Here, we assess the SARS-CoV-2 antibody dynamics prior and one month following transplantation Methods: Previously immunized wait-listed patients (2 mRNA vaccine doses: mRNA-1273 or BNT162b2 at least 14 days prior to KT) who subsequently underwent KT were included. Serum was collected within 24 hours prior to transplantation and 3-4 weeks following transplantation. ELISAs measuring anti-S and anti-RBD titers on pre- and post-transplant samples were performed. Serial dilutions of patient samples were prepared and AUC were calculated for paired samples from each participant. Paired samples were run simultaneously to reduce the effect of interplate variability. Wilcoxon and Mann-Whitney test were used to compare paired and unpaired samples, respectively Results: 35 patients were included (12 LKT/23 DDKT). 34 patients received induction with ATG, 1 with Basiliximab. Standard immunosuppression consisted of prednisone (2-week taper), mycophenolate and tacrolimus. 61% received mRNA- 1273 and 39% BNT162b2. We found no difference in Abs between vaccines. Anti- RBD Ab and anti-S Ab had a significant decline following KT at the one-month endpoint (anti-RBD Pre-KT: 1581 vs Post-KT: 473 p<0.0001 anti-S Ab Pre-KT: 4058 vs 1739 p<0.0001). 29 wait-listed patients were on dialysis and had lower pre-transplant Abs (anti-RBD dialysis: 1508 vs no dialysis: 3790 p=0.5. Anti-S Ab dialysis: 3841 vs no dialysis: 10058 p=0.17). The differences remained post-KT. 3 patients developed COVID-19 following transplantation (median: 123 days). They had lower pre- and post-transplant Ab (post-transplant anti-RBD COVID-19: 181 vs no COVID-19: 486 p=0.3, anti-S COVID-19: 1672 vs no COVID-19: 613 vs no COVID-19: 1801 p=0.4) Conclusion(s): Induction immunosuppression followed by standard immunosuppression led to a significant decrease of both anti-S and anti-RBD ab in KT recipients. Waitlisted individuals on dialysis had lower Abs both pre-and post-transplant. Patients who developed post KT COVID-19 had lower Ab levels. Our data suggests that immediate post-transplant KTs may require additional vaccinations against COVID-19.

14.
American Journal of Transplantation ; 22(Supplement 3):765, 2022.
Article in English | EMBASE | ID: covidwho-2063418

ABSTRACT

Purpose: SARS-CoV-2 is associated with high mortality among transplant recipients. This study aims to compare the humoral responses between the Oxford-Astra- Zeneca(AZ) and BNT162b2(Pfizer-BioNTech) vaccines in transplant recipients Methods: We recruited 920 kidney and SPK transplant patients receiving at least one dose of SARS-CoV-2 vaccine excluding patients with virus pre-exposure. Serological status was determined using the COVID-SeroKlir ELISA (Kantaro-EKF). Patients with corrected antibody level less than 0.7AU/mL were considered seronegative. Result(s): 495 AZ and 141 Pfizer patients had a sample post-first and 593 post-second dose (346 AZ vs 247 Pfizer) analysed. Following the 1st dose 25.7% of patients seroconverted (26.6% AZ and 22.8% Pfizer). Post-second dose 42.8% of AZ patients seroconverted (148/346) compared to 52.6% of Pfizer (130/247, p=0.02, HR 1.48, CI 1.07-2.06). When negative responders were excluded, Pfizer patients were shown to have a significantly higher response than AZ patients (median 2.6 vs 1.78AU/ mL, Mann-Whitney p=0.005), still lower than the one observed in general population. Patients on mycophenolate had a reduced seroconversion rate (42.2% vs 61.4%, p=0.001, HR 2.17) and reduced antibody levels (0.47 vs. 1.22 AU/mL, p=0.001) and this effect was dose dependent (p=0.05). Prednisolone reduced the seroconversion rate from 58.2% to 43.6% (p=0.03,HR 1.8) among Pfizer but not AZ recipients. This result was internally validated in two time points. Regression analysis has shown that antibody levels were reduced by older age (p=0.002), mycophenolate (p=0.001), AZ vaccine (vs Pfizer) (p=0.001) and male gender (p=0.02). There was no difference on infection rate post 2nd dose among the two vaccines but 14/15 serious post-vaccine infections leading to admission occurred to patients who did not seroconvert. Conclusion(s): Both seroconversion and antibody levels are lower following AZ compared to Pfizer vaccinated transplant patients following two vaccine doses. Mycophenolate, older age, male gender are also factors affecting the antibody response. Serious post vaccine infections are limited to patients without antibody response. Transplant patients remain at serious risk of SARS-CoV-2 infection.

15.
American Journal of Transplantation ; 22(Supplement 3):439, 2022.
Article in English | EMBASE | ID: covidwho-2063401

ABSTRACT

Purpose: Transplant recipients have worse CoVID-19 survival compared to the general population, and thus are recommended to be vaccinated and boosted. Determinants of vaccination efficacy have not been well studied in heart transplant patients. Method(s): This was a prospective study of heart transplant recipients vaccinated against SARS-CoV-2 with one of the 2-dose mRNA vaccine series. Antibodies (Ab) were quantified by anti-Spike ELISA pre- and post-vaccination. Clinical data was extracted from electronic medical records. Differences in Ab detection and timing of Abs were assessed for statistical significance using Fisher's exact tests for categorical variables and t-tests for continuous variables. Result(s): Of the total 54 participants recruited from Jan 2021 to present, 6 patients were Ab positive prior to vaccination and 11 did not provide a pre-vaccination sample but were Ab positive post-vaccination. Almost half of participants (48%, n=26) received a booster 3rd dose. The mean age at vaccination was 58 +/- 11, 20% (n=11) were female, 70% (n=38) were Caucasian, and median time since transplant was 4 years (interquartile range: 2-11 years). Of the 37 Ab-negative individuals enrolled, none developed detectable Abs after a single vaccine dose and only 9 (24%) developed Abs after the 2nd vaccine dose. Interestingly in this small group, 6/9 (66%) of participants had delayed seroconversion of approximately 3 months. Unexpectedly, hyperlipidemia was positively associated with a detectable antibody response (p = 0.05) after the 2nd dose. There was also a trend toward higher age (p=0.06) and BMI (p=0.08) being associated with lack of response to the 2-dose series. Importantly, of the 28 patients who had no Ab response to the 2-dose vaccination regimen, 11/17 (65%) became Ab positive after the booster, increasing the vaccine response rate in this pre-vaccine Ab-negative group to 20/37 (54%). Looking at the total cohort of 54 participants, the overall positivity rate regardless of antigen sources (i.e., including those previously infected or for whom no pre-vaccine sample is available) is 68.5% (37/54) with a trend suggesting that absence of Ab response may be associated with prednisone treatment (p=0.06). Conclusion(s): Heart transplant recipients exhibit a low response rate to the initial 2-dose mRNA vaccines (24%), but the 3rd dose induces a response in the majority of those who failed to respond to the 2-dose series increasing overall response to over 50%. Similar to observations in the general public, non-response tended to be associated with older age and higher BMI. However, further/larger studies are needed to identify key determinants of vaccine efficacy in this population to guide management.

16.
American Journal of Transplantation ; 22(Supplement 3):443, 2022.
Article in English | EMBASE | ID: covidwho-2063389

ABSTRACT

Purpose: SARS CoV-2 vaccination elicits both robust humoral and T-cell immune responses in healthy individuals. However, a comprehensive assessment of immune responses to SARS-CoV-2 vaccination in renal allograft recipients is variable and dependent primarily on Spike IgG levels. Here, we analyzed the humoral and T-cell responses in vaccinated transplant recipients. Method(s): 61Tx patients maintained either on Tacrolimus (TAC, 32) or Belatacept (BELA, 29) who were greater than one month post 2nd dose of the Pfizer BNT162b2, and 41 healthy individuals were enrolled. Fresh whole blood was incubated with SARS CoV-2 Spike peptides pool and the activated CD4+ (IL-2/TNF-alpha)+ and CD8+ (TNF-alpha/IFN-gamma)+ T cells were enumerated by flow cytometry and defined as CoV-2-specific T cells. Plasma was analyzed for Spike Receptor Binding Domain (RBD)-specific IgG by ELISA. The Spike RBD-specific IgG levels and Spikespecific CD4+/CD8+ T-cell immune responses were analyzed in TAC- and Bela- Tx patients along with healthy controls. Result(s): Our data demonstrated poor Spike IgG and T cell immune responses in Tx patients1M post-2nd dose of vaccine (21% v. 93% in positive Spike IgG and 37% v. 88% in positive T cell responses, Tx v. controls, respectively). However, 34% of Spike IgG (-) patients demonstrated positive CD4+ and/or CD8+ T-cell immune responses. No significant difference in T cell immunity was found between TAC and BELA treated patients. Conclusion(s): Immunocompromised Tx patients demonstrated significant defects in humoral and T cell immune response after vaccination. Patients maintained on TAC v. BELA demonstrated similar depressions in immune responses post-vaccination. 34% of vaccinated Tx patients, demonstrated Spike-specific T cell immunity despite being Spike IgG negative. This is suggestive of a divergent immune response with dominant cellular immunity. These observations are important since activation of T-cell immunity early after exposure to SARS-CoV2, while not preventing infection will likely modify severity of disease. (Table Presented).

17.
American Journal of Transplantation ; 22(Supplement 3):441, 2022.
Article in English | EMBASE | ID: covidwho-2063376

ABSTRACT

Purpose: To evaluate post-vaccination cellular and antibody (Ab) immunity after COVID-19 vaccination in single blood samples from 17 kidney transplant (KT) recipients who had received COVID-19 vaccination Methods: We measured frequencies of peripheral blood T- and B-cells which expressed the inflammatory marker CD154 after overnight stimulation with peptide mixtures representing the spike protein S, its S2 component which is conserved between SARS-CoV-2 and human coronaviruses, and the S1 component, which is specific to SARS-CoV-2 and also contains its receptor binding domain (RBD). Serum from each sample was assayed for anti-RBD and anti-S IgG Abs with ELISA. Optical density at 450nm (OD450) of 0.45 or greater implied presence of either Ab. Frequencies of monocytic and polymorphonuclear (PMN) myeloid-derived suppressor cell were also measured with flow cytometry. Result(s): Median age was 40 yrs (range 25 to 83), male:female gender distribution was 7:8. All recipients received mRNA vaccination. Anti-S-IgG and anti-RBD-IgG were detected in 11 (Ab+) and were absent in four (Ab-). Compared with Ab+ KT recipients, those who were Ab- had lower frequencies of S2-reactive and S-reactive B-cells (p<0.05), CD4+ and CD8+ T-cells (Table 1, Fig 1). S1-reactive T-cell and B-cells were non-detectable. Frequencies of PMN-MDSC were numerically higher in Ab- compared with Ab+ KT recipients (Mean +/- SEM 38.9+/-8.1 vs 19.4+/-1.8, p-value 0.1, NS). Significant negative correlation was observed between PMN-MDSC frequencies and strength of anti-RBD IgG and anti-SPIKE IgG (Fig 1). Conclusion(s): COVID-19 vaccination results in spike antigen reactive T- and B-cells in KT recipients who develop Abs after vaccination. Failure of an Ab response is associated with impaired B-cell responses to the spike antigen and an increase in circulating polymorphonuclear myeloid derived suppressor cells. (Table Presented).

18.
American Journal of Transplantation ; 22(Supplement 3):458-459, 2022.
Article in English | EMBASE | ID: covidwho-2063349

ABSTRACT

Purpose: The diverse factors affecting the vaccine induced neutralizing antibody response in solid organ transplant recipients and their immunity against CoV2 variants are needed to be well characterize to understand how we improve the vaccine efficacy. Method(s): Anti-CoV2 receptor binding domain (RBD) plasma antibody response and their neutralization potency in 29 kidney and 22 heart transplant patients was determined with recombinant RBD protein binding ELISA and by calculating the 50% virus neutralization titer of the plasma antibody with ACE2-Hu-HeLa cell based pseudo virus neutralization assay against CoV2 wild type and delta variant. Result(s): We detected strong binding and protective neutralizing plasma antibody response in SOTR who were infected with CoV-2 either prior to or after the first dose of vaccine (n=8), who showed high median IC50 value > 10,000 against both the CoV2 wild type strain and the more transmissible delta variant. In contrast to this, the CoV2 uninfected and vaccinated SOTR ( naive vaccinees, n=43) had considerably lower anti-RBD plasma antibody binding titers, and only 19% of this population possessed minimally protective neutralizing antibody titer (IC50 >50) against the wild type CoV2 strain, which further decreased to 10% against the delta variant. While IgG and IgA were dominant isotypes of anti-RBD antibody induced by the CoV2 vaccines and correlated significantly (r=0.84, p=<0.001) with the CoV2 neutralization. The COV2 uninfected SOTR vaccinees who were within 1.5 years from transplantation or African American ethnicity were less likely to have detectable vaccine induced neutralizing antibody responses than the other populations. In the naive vaccinees, administration of corticosteroids in combination with calcineurin or mTOR inhibitors and antimetabolites also negatively affected the CoV2 antibody responses, while female and younger organ transplant recipients tended towards higher IgM and IgA titers. Kidney transplant recipients showed better IgG responses vs heart transplant recipients and elevated serum creatinine levels correlated with poorer antibody response to the vaccines in both kidney and heart transplant groups. Conclusion(s): These results suggest that in the absence of immunity due to CoV2 infection, vaccination in SOTRs induces much lower protective antibody levels than in healthy controls and identifies African-American ethnicity, less than 1.5 years post transplantation as additional risk factors that further exacerbate these effects. Poor kidney function negatively affected the vaccine induced antibody response.

19.
American Journal of Transplantation ; 22(Supplement 3):597, 2022.
Article in English | EMBASE | ID: covidwho-2063338

ABSTRACT

Purpose: To investigate the effect of mycophenolate mofetil (MMF) on SARSCoV- 2 vaccination response in kidney transplant recipients using the standard immunosuppressive regimen of tacrolimus (TAC) and MMF. Method(s): A randomized controlled trial in immunologically low risk kidney transplant recipients was performed (EudraCT nr.: 2014-001372-66). Patients were randomized to standard TAC/MMF or TAC monotherapy (TACmono) from 9 months onwards, without steroids. Antibody based immune responses to SARS-CoV-2 vaccination (mRNA-1273 or BNT162b2) were investigated in a central laboratory, as part of the RECOVAC Antibody study (EudraCT nr.: 2021-283 001520-18), 4-8 weeks after the second vaccination. Measurement involved the presence of antibodies against the receptor binding domain (RBD) of the SARS-CoV-2 S-protein (IgG anti-RBD antibody) using the Sanquin anti-SARS-CoV-2 RBD IgG ELISA assay. Patients were classified as non-responders (<=50 BAU/mL), low-responders (50-300 BAU/ mL) and responders (>300 BAU/mL). Result(s): Between 2015 and 2018, 79 recipients were randomized to TAC/MMF (n=41) and TACmono (n=38). At the outbreak of the COVID-19 pandemic in early 2020, 67 patients were alive with a functioning graft (TAC/MMF n=35, TACmono n=32). In 27 patients antibody responses could be established: Ten patients were excluded from the analyses due to symptomatic COVID-19 infection and 1 due to a positive nucleocapsid test, possibly from an asymptomatic infection. The rest did not participate in the vaccination study, because of ChAdOx1-S, age >80 years or lack of informed consent. Mean age was 64 (43-75) years, median time after transplantation 4.2 (3.0-6.5) years and eGFR was 53 (36-105) ml/min/1.73m2. TAC trough levels were 6.6 (+/-0.3) mug/L in both groups, and MMF dose was 1000 mg daily (range 500- 2000) in TAC/MMF. Median SARS-CoV-2 Spike S1-specific IgG antibody levels were 37.3 BAU/ml in TAC/MMF (5 non, 7 low, 1 responder) and 715.6 BAU/ml in TACmono (1 non, 6 low, 7 responders, p =0.004, figure 1). Of note is that antibody levels of >1000 BAU/ml, as a presumed threshold for protection against Omicron (B.1.1.529), was reached in 1/13 TAC/MMF and 7/14 TACmono patients (p=0.03). Conclusion(s): In this controlled study mycophenolate mofetil on top of tacrolimus severely hampered serological COVID-19 vaccination response.

20.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-344474

ABSTRACT

Background: The impact of chronic health conditions (CHC) on serostatus post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is unknown. Method(s): We assessed serostatus post-SARS-CoV-2 vaccination among fully vaccinated adult residents of Jefferson County, Kentucky, USA from April 2021 through August 2021. Serostatus was determined by qualitative analysis of SARS-CoV-2 specific Spike IgG antibodies via enzyme-linked immunoassay (ELISA) in peripheral blood samples. Result(s): Of the 5,178 fully vaccinated participants, 51 were seronegative and 5,127 were seropositive. Chronic kidney disease (CKD) and autoimmune disease showed highest association with negative serostatus in fully vaccinated individuals. The absence of any CHC was strongly associated with positive serostatus. The risk of negative serostatus increased as the total number of pre-existing CHCs increased. Similarly, use of 2 or more CHC related medications was associated with seronegative status. Conclusion(s): Presence of any CHC, especially CKD or autoimmune disease, increased the likelihood of seronegative status among individuals who were fully vaccinated to SAR-CoV-2. This risk increased with a concurrent increase in number of comorbidities, especially with multiple medications. Absence of any CHC was protective and increased the likelihood of a positive serological response. These results will help develop appropriate guidelines for booster doses and targeted vaccination programs. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

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